Induction of carbohydrate‐specific antibodies in HLA‐DR transgenic mice by a synthetic glycopeptide: a potential anti cancer vaccine for human use

Abstract: Over the last few years, anticancer immunotherapy has emerged as a new exciting area for controlling tumors. In particular, vaccination using synthetic tumor‐associated antigens (TAA), such as carbohydrate antigens hold promise for generating a specific antitumor response by targeting the immune system to cancer cells. However, development of synthetic vaccines for human use is hampered by the extreme polymorphism of human leukocyte‐associated antigens (HLA). In order to stimulate a T‐cell dependent anticarbohydrate response, and to bypass the HLA polymorphism of the human population, we designed and synthesized a glycopeptide vaccine containing a cluster of a carbohydrate TAA B‐cell epitope (Tn antigen: α‐GalNAc‐Ser) covalently linked to peptides corresponding to the Pan DR ‘universal’ T‐helper epitope (PADRE) and to a cytotoxic T lymphocyte (CTL) epitope from the carcinoembryonic antigen (CEA). The immunogenicity of the construct was evaluated in outbred mice as well as in HLA transgenic mice (HLA‐DR1, and HLA‐DR4). A strong T‐cell dependent antibody response specific for the Tn antigen was elicited in both outbred and HLA transgenic mice. The antibodies induced by the glycopeptide construct efficiently recognized a human tumor cell line underlying the biological relevance of the response. The rational design and synthesis of the glycopeptide construct presented herein, together with its efficacy to induce antibodies specific for native tumor carbohydrate antigens, demonstrate the potential of a such synthetic molecule as an anticancer vaccine candidate for human use.     

重组人纽表位肽12生物学活性测定方法的研究

目的：建立适用于重组人纽表位肽12体外质量控制的生物学活性测定方法，用于该制品的生物学活性评价。方法：采用小鼠，比较不同品系、给药浓度、给药周期等条件下应用ELISA方法检测出的小鼠相应抗体水平，确定最佳实验条件，以建立相应的体外活性测定方法。结果：FVB／N转neu基因小鼠(TgN MMTVneu202 Mul，Jackson Lab．，USA)对重组人纽表位肽12的反应存在量——效关系，并确定了最佳测定条件和给药剂量，用抗体阳转百分率作为评价指标，样品测定重复性较好，CV％值为6．7％(H=4)，结果可靠。结论：已建立的FVB／N转neu基因小鼠测定重组人纽表位肽12生物学活性的方法可用于重组人纽表位肽12生物学活性的常规评价。     

商标及其翻译的文化传播功能

随着改革开放的进一步深化,大量的国际知名产品涌入国内市场.同时,伴随着国内产品竞争力的不断提升,许多 产品也正在走向国际市场.商标作为商品经济的产物,它的翻译备受关注,并且亦已进入语言学界研究的视野.该 文就国内市场上一些著名英语商标品牌词语的翻译和其所包涵的文化寓意,进行了有益的探讨,以期为我国的产 品能更好地进入国际市场提供一些建议.     

铺灸疗法为主治疗强直性脊柱炎的Meta分析

目的：评价铺灸疗法治疗强直性脊柱炎（AnkylOSingSpondylitiS,AS）疗效的优越性、远期疗效及安全性。方法：计算机检索从2000年到2012年在中国知网（CNKI）、万方数据库（WF）中收录的有关铺灸疗法为主治疗AS的随机对照试验（randomizedcontrolledtrial,RCT）文献,对文献进行质量评价,并用ReviewManager5．1软件进行荟萃分析（Meta分析）。结果：总共纳入临床随机对照试验文献17篇,涉及患者共1700名。Meta分析结果显示铺灸疗法治疗强直性脊柱炎的总体有效率优于口服西药疗法和单纯针刺疗法。与口服西药疗法比较,合并后效应指标RR=I．24,95％（ConfidenceInterval,CI）为（1．14,1．35）;与针刺疗法比较,合并后效应指标RR=I．27,95％CI（1．05,1．53）。结论：此次纳入研究丈献质量普遍偏低：全部为单中心RCT研究,无多中心研究。其次,随机分组方法不够准确,多数文献未描述随访、脱落、远期疗效情况,诊断标准、疗效评价指标种类繁多,未能采取国际公认的标准。与口服西药疗法比较,铺灸疗法的总体有效率远高于12服西药疗法,疗效优越且复发率较低,无毒副作用,安全可靠;和针刺疗法比较,虽然药物铺灸疗法总体有效率较高,由于纳入研究数目较少,总病例数亦少,无远期疗效和安全性方面对比,其结果有待于大样本、多中心、方法科学的高质量临床研究加以验证。     

黄热病毒特异性抗原片段的筛选与鉴定

目的通过系统的生物信息学分析和实验验证,筛选黄热病毒的特异抗原片段,为免疫诊断试剂的研制奠定基础。方法分别利用DNAStar及ANTHEPROT软件对黄热病毒蛋白进行分析,参考亲水性、抗原性、可塑性、表面可及性及二级结构信息,对黄热病毒可能的共有及特异性抗原表位进行系统的预测分析,分析其在不同毒株中的保守性,并对预测得分值较高的抗原区域进行RT-PCR扩增,利用pMal-c2x原核表达系统进行原核表达,Western blot验证其免疫学反应原性,检测阳性抗原片段经亲和纯化后,包被ELISA微孔板,进一步验证其免疫学反应特异性及检测敏感性。结果其中27段抗原片段获高效表达,经Western blot筛选及ELISA进一步验证,原核表达抗原片段YFV22表现良好特异抗,可检测低至1∶12 800倍稀释的黄热病毒多克隆抗体,与所试其他参考病毒多克隆抗体无交叉反应。结论经系统筛选、验证,获黄热病毒特异性抗原片段1段,为其免疫学诊断试剂的研制奠定了基础。     

Antigenicity Alternations of Variant PEDV S Protein Disclosed by Linear B Cell Epitope Mapping

The spike protein (S) plays a crucial role in porcine epidemic diarrhea virus (PEDV) infection and induces neutralizing antibodies. Mutations of the S protein are supposed to provide the main antigenic shift leading to the antigenic escape of PEDVs. It is therefore a significant question how much accumulation of antigenic shift could lead to the antigenic escape of the variant PEDV. To provide an answer in the study, B cell epitopes (BCEs) on the S protein of the PEDV vaccine strain CV777 (S^CV777) and variant strain SD2014 (S^SD2014) were mapped using biosynthetic peptides and rabbit anti-PEDV S serum. Seventy-nine and 68 linear BCEs were identified from S^CV777 and S^SD2014, respectively. While 66.2% of the BCEs of S^SD2014 could be recognized by anti-S^CV777 serum and 67.1% of S^CV777 BCEs could be recognized by anti-S^SD2014 serum, more than 40% of the BCEs identified using anti-S^CV777 serum on S^CV777 could not be recognized by anti-S^SD2014 serum and vice versa. The completely shared BCEs took low percentages of 29.4% and 25.3% for S^SD2014 and S^CV777, respectively. These results indicate a low conservation of antigenicity of the S protein compared to a relatively high amino acid sequence similarity of 92.2% between the two strains. The study provided a BCE shift reference of PEDV antigenic escape and surveillance control.     

手法整复闭合穿针内固定配合外敷促愈膏治疗尺桡骨骨折

目的:观察尺桡骨骨折采用手法整复,闭合穿针内固定,配合外敷促愈膏的疗效。方法:手法整复,闭合穿针内固定配合外敷促愈膏。结果:治疗不稳定性尺桡骨骨折28例,愈后良好占88.5%。结论:此方法操作简单,创伤小,费用低,疗效好。     

Major carbohydrate epitopes in tissues of domestic and African wild animals of potential interest for xenotransplantation research

Oriol R, Candelier J‐J, Taniguchi S, Balanzino L, Peters L, Niekrasz M, Hammer C, Cooper DKC. Major carbohydrate epitopes in tissues of domestic and African wild animals of potential interest for xenotransplantation research. Xenotransplantation 1999; 6: 79‐89. ©Munksgaard, Copenhagen.
Abstract: we investigated the main glycotopes expressed on the tissues of 44 animal species, including primates, nonprimate mammals, marsupials, birds, and a reptile. Paraffin‐embedded tissue sections of kidney, heart, liver, pancreas, lung, brain and intestine of 24 domestic animal species were stained with seven fluorescent‐labeled lectins. Testis sections of 20 African wild animal species were tested with the same lectins. Overall, three main immunofluorescence patterns were found in the vascular compartment. First, humans and Old World monkeys express genetically polymorphic ABH antigens and do not express αGal. Second, New World monkeys, other mammals, and marsupials do not express ABH antigens, but have large amounts of a genetically monomorphic αGal. Third, birds and reptiles do not express either ABH or αGal, but have monomorphic βGal, probably different from the lactosamine precursor of ABH and αGal. Epithelial cells producing exocrine secretions also expressed carbohydrate epitopes. The fluorescence patterns of the cells of the exocrine compartment are similar, but not identical, to those expressed in the vascular compartment. All the animals tested have some ABH and βGal in exocrine tissues, but New World monkeys and lower mammals are the only ones expressing αGal in exocrine tissues.     

埃博拉病毒NP抗原表位区段的克隆和表达

目的分析埃博拉病毒核蛋白（ NP）抗原表位,克隆表达埃博拉病毒NP抗原,为免疫学诊断试剂的研究奠定基础。方法采用BioSun生物学软件预测分析埃博拉病毒NP抗原的氨基酸表位区间,采用大肠杆菌优势密码子反向翻译成基因序列,采用PCR退火合成法合成NP优势密码子抗原基因,并利用载体pBVIL1进行克隆表达。采用间接ELISA技术评价获得NP抗原的特异性。结果确定埃博拉病毒NP抗原的氨基酸表位位于360～739 aa,共设计36条引物,扩增合成1140 bp的NP抗原基因,克隆表达后,融合蛋白相对分子质量为58×103,测序结果显示插入的NP基因正确。初步结果显示,NP抗原的特异性为99．24％（130／131）。结论获得埃博拉病毒NP抗原,为进一步研制特异的埃博拉病毒快速诊断试剂提供了抗原储备。